Abstract
Abstract Dysfunction of adipocytes and adipose tissue is a primary defect in obesity and obesity-associated metabolic diseases. Interferon regulatory factor 3 (IRF3) has been implicated in adipogenesis. However, the role of IRF3 in obesity and obesity associated disorders still remains unclear. Here we show that IRF3 expression in human adipose tissue was positively associated with insulin sensitivity and negatively associated with type 2 diabetes. In mouse preadipocytes, IRF3 not only acts as a brake negatively regulating the adipogenic transcriptional network centered on the PPARg pathway, but also is important for the functionality of adipocytes. In macrophages, IRF3 inhibits inflammatory cytokine expression through IFNb/IL-10 axis, thereby restraining adipose tissue inflammation in obesity. Mice deficient in IRF3 developed obesity and type 2 diabetes spontaneously associated with increased adipose tissue inflammation. This study demonstrates that IRF3 regulates the biology of multiple cell types including adipocytes and macrophages to prevent the development of obesity and obesity-related complications, hence, could be a target for therapeutic interventions for prevention and treatment of obesity-associated metabolic disorders. National Medical Research Council of Singapore
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